title: Novel mutations in ataxia telangiectasia and AOA2 associated with prolonged survival.
abstract: Ataxia telangiectasia (AT) and ataxia oculomotor apraxia type 2 (AOA2) are autosomal recessive ataxias caused by mutations in genes involved in maintaining DNA integrity. Lifespan in AT is greatly shortened (20s-30s) due to increased susceptibility to malignancies (leukemia/lymphoma). Lifespan in AOA2 is uncertain. We describe a woman with variant AT with two novel mutations in ATM (IVS14+2T>G and 5825C>T, p.A1942V) who died at age 48 with pancreatic adenocarcinoma. Her mutations are associated with an unusually long life for AT and with a cancer rarely associated with that disease. We also describe two siblings with AOA2, heterozygous for two novel mutations in senataxin (3 bp deletion c.343-345 and 1398T>G, p.I466M) who have survived into their 70s, allowing us to characterize the longitudinal course of AOA2. In contrast to AT, we show that persons with AOA2 can experience a prolonged lifespan with considerable motor disability.
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA, United States.
authors.forename: Marie Y
authors.initials: MY
authors.lastname: Davis
authors.forename: C Dirk
authors.initials: CD
authors.lastname: Keene
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Swanson
authors.forename: Conor
authors.initials: C
authors.lastname: Sheehy
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bird
mesh_terms: D000328:Adult; D000368:Aged; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D064026:Calbindins / Q000378:metabolism; D004265:DNA Helicases; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D064251:Multifunctional Enzymes; D009154:Mutation / Q000235:genetics*; D020365:RNA Helicases / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D064026:Calbindins; D064251:Multifunctional Enzymes; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases
keywords: AOA2; AT; ATM; Ataxia; Ataxia oculomotor apraxia type 2; Ataxia telangiectasia; SETX; Senataxin